Project Summary/Abstract Background: Antibiotic overuse threatens patient safety by causing adverse effects and threatens the effectiveness of antibiotics through the development of antibiotic resistance. However, studies to describe and interventions to address these safety risks have focused on visit-based antibiotic prescribing. Non-visit-based antibiotic use and prescribing has been largely invisible. In preliminary work, we found that 23% of patients who received an antibiotic prescription did not have an office visit in the study year. We have also found that clinicians prescribed 39% of antibiotic prescriptions on days when patients did not have visits. Non-visit-based antibiotic fills by patients and prescribing by clinicians may contribute to patients' risk of adverse events and hasten the spread of antibiotic resistance, but non-visit-based antibiotic prescribing has not been measured. Research Strategy: To measure and describe the safety risk and antibiotic resistance pressure from contemporary non-visit-based antibiotic use in the United States, we propose complementary specific aims using claims data and electronic health record (EHR) prescribing data. Our main hypotheses are that 1) non- visit-based antibiotic prescribing accounts for a significant proportion (>20%) of antibiotic use and 2) the majority (>50%) of non-visit-based antibiotic use is untethered to a proximate clinic visit or a chronic, recurrent problem. To address these hypotheses and plan for future interventions, we have 3 Specific Aims. Specific Aim 1 is to perform a retrospective cohort study of medical and prescription drug claims of care received by over 10 million commercial health plan and 50 million Medicaid enrollees to measure and describe non-visit- based antibiotic prescription fills relative to all antibiotic fills. Specific Aim 2 is to perform a cohort study of electronic health record (EHR) prescribing to measure and describe non-visit-based antibiotic prescribing as well as conduct a mixed-methods study of EHR data and qualitative interviews with clinicians to understand the rationales for non-visit-based antibiotic prescribing. Specific Aim 3 is to use the results of the national study, cohort study, and mixed-methods sub-study to develop an evidence-based toolkit that can be used by other clinicians, health systems, payors, and stakeholders to measure and address non-visit-based antibiotic use. Implications and Future Directions: In the near term, this project will open a novel research front, quickly expanding our understanding of antibiotic use in the United States. In the longer-term ? at a time when the US health care system is moving towards less visit-based care ? this project will lay the foundation for interventions to encourage judicious antibiotic prescribing and use, even in the absence of clinic visits. The ultimate goal of this project and subsequent interventions is to preserve antibiotic effectiveness, limit the spread of antibiotic-resistant bacteria, and to promote patient safety in ambulatory settings.